Alzheimer's disease is a devastating disorder that strikes 1 in 10 Americans over age 65 and almost half of Americans over 85. The odds of developing Alzheimer's disease double every five years after age 65. While it is increasingly common to meet heart attack or cancer survivors, it is impossible to meet an Alzheimer's disease survivor because there are none. The Center of Excellence for Research on Complementary and Alternative Medicine (CERC) in Alzheimer's disease is a joint effort from investigators at Mount Sinai School of Medicine (MSSM), the Purdue University Botanical Research Center and collaborating institutions defines our vision for an integrated multidisciplinary program of preclinical research projects all linked by a unifying scientific theme related to the understanding of the potential protective roles of grape-derived polyphenols in Alzheimer's disease. There is mounting evidence that grape-derived polyphenols may beneficially influence Alzheimer's disease. However, because polyphenolic compositions and bioactivities vary considerably due to plant-growth environments, there are problems with the preparation of grape-derived polyphenols (and other dietary polyphenols). These limitations have prompted us to assemble groups of interdisciplinary scientists with expertise in Alzheimer's disease and nutritional-botanical sciences to design a series of studies with the ultimate goal of isolating and identifying, from dietary grape sources, bioactive and bioavailable polyphenolic compounds that are capable of providing beneficial Alzheimer's disease-modifying activities. Significant discoveries on the beneficial role of dietary polyphenolics in the prevention of Alzheimer's disease through the attenuation of (3-amyloid pathogenesis is providing new knowledge in novel pathogenic mechanisms and the possibility of novel potential solutions. The studies and the information that would be gleaned from this proposal are precisely on target to provide these insights. We are confident that the information that will come from this work will have a major impact on protective roles of grapederived polyphenols in Alzheimer's disease.